RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation.

Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti-metastatic drugs are still limited. Here it is reported that the RNA-binding protein RBMS1 is positively associated with increased lymph node metastasis in non-small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.

Prediction models of fire spread rate of Pinus koraiensis plantation's surface fuel.

Pinus koraiensis plantation has high fire risks due to high oil content in branches and leaves. The spread of surface fire is the main way of forest fire expansion. Understanding the surface fire spread rate can provide scientific guidance for fire fighting. We carried out a laboratory experiment with surface fuel of Pinus koraiensis plantation in Maoershan area of Heilongjiang Province. We set different levels of fuel moisture contents (5%, 15%, 25%), fuel loads (0.5, 0.7, 0.9, 1.1 kg·m-2), and slope (0°, 10°, 20°, 30°, 40°) to simulate the characteristics of fuel bed in the field, and quantified the spread rate by thermocouple method. We further compared and analyzed the prediction accuracy of Rothermel model, modified Rothermel model and random forest model, and evaluated the optimal model for predicting the surface fire spread rate of P. koraiensis plantation. The results showed that the overall efficacy of directly using the Rothermel model to predict the surface fire spread rate of P. koraiensis plantations was good, but the prediction result of the spread rate under the conditions of high slope and high moisture content was not satisfied. The Rothermel model after refitting the slope parameters and the random forest model had good prediction efficacy and similar prediction accuracy. The random forest model needed to be further evaluated and verified due to its own characteristics. The modified Rothermel model was more suitable for predicting the surface fire spread rate of P. koraiensis plantations at a slope range of 0°-40° than the others.

Loss of RBMS1 promotes anti-tumor immunity through enabling PD-L1 checkpoint blockade in triple-negative breast cancer.

Immunotherapy has been widely utilized in multiple tumors, however, its efficacy in the treatment of triple-negative breast cancers (TNBC) is still being challenged. Meanwhile, functions and mechanisms of RNA binding proteins in regulating immunotherapy for TNBC remain largely elusive. Here we reported that the RNA binding protein RBMS1 is prevalent among immune-cold TNBC. Through a systematic shRNA-mediated screen, we found depletion of RBMS1 significantly reduced the level of programmed death ligand 1 (PD-L1) in TNBC. Clinically, RBMS1 was increased in breast cancer and its level was positively correlated to that of PD-L1. RBMS1 ablation stimulated cytotoxic T cell mediated anti-tumor immunity. Mechanistically, RBMS1 regulated the mRNA stability of B4GALT1, a newly identified glycosyltransferase of PD-L1. Depletion of RBMS1 destabilized the mRNA of B4GALT1, inhibited the glycosylation of PD-L1 and promoted the ubiquitination and subsequent degradation of PD-L1. Importantly, combination of RBMS1 depletion with CTLA4 immune checkpoint blockade or CAR-T treatment enhanced anti-tumor T-cell immunity both in vitro and in vivo. Together, our findings provided a new immunotherapeutic strategy against TNBC by targeting the immunosuppressive RBMS1.

Lysimachia christinae Hance regresses preestablished cholesterol gallstone in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Whole herb of Lysimachia christinae has long been used as a remedy for cholelithiasis extensively in China. This study was aimed to validate the effect of L. christinae on eliminating preestablished cholesterol gallstone (CGS) in model animals. MATERIALS AND METHODS: Acute toxicity of aqueous extract of L. christinae (LCAE) was estimated in male C57BL/6 mice, so was the efficiency of LCAE on preformed CGS induced by lithogenic diet. The effects of LCAE were also examined on bile secretion rate, the lipid profiles of bile and serum, body weight, main visceral organ indexes, and histomorphology of main visceral organs. RESULTS: Single dose of LCAE did not lead to death and changes on body weight gain, main visceral organ indexes, histomorphology of main visceral organs, and blood hemogram and biochemical indexes, even at dose of 50g material/kg body weight. Preestablished CGSs were almost entirely eliminated after administration of LCAE for 2wk at high dose or for 4wk at low dose. LCAE promoted bile secretion and lowered cholesterol levels in either cystic bile or hepatic bile. LCAE also decreased serum cholesterol content, especially LDL-C content, tremendously, reduced the levels of serum HDL-C, phospholipid, and triglycerine a little, and lowered body weight and liver index significantly. After medication of LCAE for 8wk , neither visceral indexes nor histomorphology of heart, kidney, and spleen were influenced, but fatty degeneration of liver induced by high fat and high cholesterol diet was reverted. CONCLUSION: L. christinae can be considered as non-toxic. It showed prominent efficiency of eliminating preexisted CGS in mice and indicated a hypolipidaemic effect.